[논문]The PDE5 inhibitor udenafil ameliorates nonalcoholic fatty liver disease by improving mitochondrial function

Yu, Hea Min; Chung, Hyo Kyun; Park, Kang Seo

doi:10.1016/j.bbrc.2021.04.038

[해외논문] The PDE5 inhibitor udenafil ameliorates nonalcoholic fatty liver disease by improving mitochondrial function

Biochemical and biophysical research communications, v.558, 2021년, pp.57 - 63

Yu, Hea Min (Division of Endocrinology and Metabolism, Department of Internal Medicine, Daejeon Eulji Medical Center, Eulji University) , Chung, Hyo Kyun (Research Institute for Medical Sciences, Chungnam National University School of Medicine) , Park, Kang Seo (Division of Endocrinology and Metabolism, Department of Internal Medicine, Daejeon Eulji Medical Center, Eulji University)

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Abstract Nonalcoholic fatty liver disease (NAFLD) refers to a series of diseases, including simple steatosis, caused by the excessive accumulation of fat in hepatocytes, nonalcoholic steatohepatitis with inflammation and fibrosis, and more advanced forms of cirrhosis. The pathogenic mechanisms underlying fatty liver and the progression from simple fatty liver to hepatitis and cirrhosis remain unclear. One potentially unifying mechanism may be a dysregulation of free fatty acid oxidation. The oversupply of fatty acids to the liver can result in mitochondrial dysfunction leading to the accumulation of lipids in the liver. Interestingly, there have been several reports showing that inhibitors of phosphodiesterase 5 (PDE5) can increase mitochondrial biogenesis, preserve mitochondrial function in vitro. And, we have recently demonstrated that the phosphodiesterase type 5 inhibitor udenafil improves insulin sensitivity by increasing mitochondrial function in adipocytes. In this study, we aimed to examine the effects of the PDE5 inhibitor udenafil on NAFLD in the ob/ob mouse model. Treatment of ob/ob mice for 6 weeks with udenafil reduced fat mass and fasting glucose. Importantly, udenafil caused a reduction in lipid accumulation in the liver of these mice, including hepatic triglyceride (TG) and cholesterol levels. Mechanistically, udenafil decreased the proinflammatory cytokines in the liver. Also, udenafil increased the levels in the liver of the important lipolytic enzymes and the levels of several mitochondrial β-oxidation related genes. Similar effects were seen in udenafil treated primary hepatocytes. We believe that our study makes a significant contribution to the literature because the results from our study suggest that udenafil may be an effective treatment for NAFLD by improving mitochondrial function. Highlights We aimed to examine the effects of the PDE5 inhibitor udenafil on non-alcoholic steatohepatitis in the ob/ob mouse model. The PDE5 inhibitor udenafil improves hepatic steatosis in vivo. The PDE5 inhibitor udenafil also increased beta oxidation and lipolysis by improving mitochondrial function in vitro.

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[해외논문] The PDE5 inhibitor udenafil ameliorates nonalcoholic fatty liver disease by improving mitochondrial function

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[해외논문] The PDE5 inhibitor udenafil ameliorates nonalcoholic fatty liver disease by improving mitochondrial function

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